Intraperitoneal injections of HK-801 were found to induce c-fos prominently in the medial thalamic nuclei including reuniens, paraventricular, mediodorsal, rhomboid, and central medial. c-fos induction was also seen in the deep layers of all neocortical regions. c-fos induction in the hippocampus, on the other hand, was blocked by MK- 801. Systemic amphetamine had a somewhat similar effect in the thalamus. Focal injections of amphetamine and MK-801 into the striatum and n. accumbens also enhanced c-fos induction in the thalamic nuclei. Micro injections of MK-801 into the nucleus accumbens as well as medial thalamus, subthalamic nucleus -and ventral tegmental area increased locomotor output in rats. Therefore, blockade of glutamate function at a variety of different relay nuclei of the basal ganglia circuits appears to be capable of locomotor excitation. Electrolytic lesions of the qlobus pallidus decreased the ability of both amphetamine and MK-801 to enhance locomotor activity.